The identification of individuals at high risk for the development of large bowel cancer prior to clinical symptoms and the incidence/hazards of mutagenesis and transformation that their somatic cells are at risk for are the dual aims of this research proposal. These two aims are subdivided into 4 working objectives: (1) to identify a culture phenotype which consistently and reliably reflects the presence of a germinal mutation in a cultured somatic cell from individuals at risk for a hereditary colorectal cancer and to use this culture phenotype to determine how this mutation (a) affects cell function and (b) is expressed in tissue specificity, a property that all hereditary tumors appear to possess; (2) to develop a model system for testing the two step hypothesis of carcinogenesis; (3) to study the mutagenesis in cell populations with and without known germinal mutations for colorectal cancer; (4) to study transformation in such genotypically abnormal cells in an attempt to evaluate the risk individuals with such genotypes run in exposure to known environmental agents inducing mutagenesis and transformation. Cell culture studies will be based on the family as the study unit.